Jennifer Sucre, MD, Assistant Professor of Pediatrics-Neonatology at Vanderbilt University Medical Center talks about her research into why COVID-19 seems to spare young children.
Tell me about your study. What did you and your colleagues look at?
Dr. Sucre: I am in a group of neonatologists and pulmonologists that study lung development. For the last several years we have been building a dataset trying to study how developing lungs in babies and children is different from adult lungs. When COVID-19 started becoming a pandemic, we noticed a few things including that babies and infants were not getting as sick as adults and this was surprising. Most respiratory illnesses severely affect neonates and children and usually people as they age do not get as sick unless they are incredibly old. Because of this paradox we wondered if there was something different about the developing lung that protected it from SARS-CoV-2 infection. So, to look at how the developing lung might be different we used our developmental dataset and started to look at host factors of epithelial cells in the lung that allow the virus to get inside. One of the things we looked at was something called ACE2 which is a receptor to the SARS-CoV-2 virus that has been well studied, and we found no differences in SARS-CoV-2 across lung development. We then looked at another co-receptor called TMPRSS2. TMPRSS2 acts as an uncorking protein to allow the virus to get inside the cell. What we found is that in a couple of specific cell types specifically the types that have modal cilia that help with clearance of mucus had more TMPRSS2 as we age. So little expression in babies and children and more expression as we get older. We saw a similar pattern in some of the cells in the organ of the lung called Type 1 epithelial cells. So, in finding this we realized that the developing lung was different than the older aged lung. To validate the findings, we looked at mice’s lung development. We also partnered with pathologists here at Vanderbilt to look at a library of lung samples from biopsy and autopsy specimens of babies all the way through older adults in their upper 60s. What we found is the same pattern of expression of this protein in epithelial cells goes up as we age.
But there are some kids that have died from COVID. Why that would happen even though they are younger, and it tends to affect older people more?
Dr. Sucre: There have been isolated case reports of children having severe illness and in general those children have other health conditions. When we look at the worldwide population there are very few children having severe symptoms of the disease.
So, how can your findings lead to a potential therapy?
Dr. Sucre: TMPRSS2 is a protein that has been well studied in other disease processes, specifically in prostate cancer and there are a couple of drugs that are approved to target that protein. We can’t make huge leaps to start treatment from this preliminary study but our hope is that we’ve provided the foundation to start investigating these drugs potentially as a prophylactic therapy when people are exposed or at high risk of exposure to COVID or as a treatment to prevent invasive disease from the virus. We also looked at patients who died from COVID infection and in the lungs of these patients we were able to find the virus sitting literally in the same cells making this TMPRSS2 protein suggesting that this may be involved in severe infection.
So, what is the next step?
Dr. Sucre: I think there are a few next steps. This is early data and while we are excited to get this story out there to allow scientists around the world to build on this foundational discovery, we would like to look at more patients. As there are more COVID patients who have tissue available to study, the next step would be to use some of these drugs that target TMPRSS2 expression to see if they can delay or prevent viral infectivity or replication and that could be done in a variety of samples. We have a lot of lung models that we use here at Vanderbilt. Some of the models we use involve making precision cut lung slices which are thin slices of lung tissue that continue to grow in culture. It provides an ideal system to study viral infection with these inhibitors to see if targeting this TMPRSS2 molecule may help prevent the spread or the invasiveness of the infection.
Can you name a few of the therapies that target TMPRSS2?
Dr. Sucre: Camostat is one of the therapies that targets TMPRSS2 and there was work during the first SARS virus that showed Camostat was able to prevent that infection. We do not know what Camostat will do with SARS-CoV-2, but it is the next place we should look.
What would your research mean for someone who is afraid right now to just live life because of COVID?
Dr. Sucre: I think that everyone has a different estimation of their personal risk. I think there are a lot of things we can do to protect ourselves and protect others. It is complicated for sure but things like wearing a mask and social distancing have been shown to flatten the curve in other countries and are practices we can all do as good citizens. I think our work speaks to the basic molecular biology and I hope that it provides scientists around the world who are using the resources of our laboratories to try to find ways to target this infection. My hope as a citizen is that we do find a cure and a vaccine soon.
How far away are we from a clinical trial?
Dr. Sucre: We have experts in the SARS-CoV-2 virus here at Vanderbilt who helped develop Remdesivir and other anti-viral infections. We are looking forward to partnering with them to see if using drugs that might target TMPRSS2 could provide a window into new therapies. Sometimes the pace of science is slow and sometimes it is accelerated, and it is an extraordinary time to be doing research when everyone is open to new and creative ideas. All of us have focused our laboratories on finding a cure for this disease so I cannot forecast a specific date. As a mother, daughter, and wife my hope is that we find a cure for this disease soon.
Is there anything I did not ask you that you feel people should know?
Dr. Sucre: I think this research really provides insight into how the lung changes from birth to aging. It allows us to understand lung development in a different way and how the keys to a developing lung can help us understand this pandemic, future pandemics, and future lung diseases across the lifespan.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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